Retinal degenerations collectively represent the leading cause of irreversible vision loss worldwide, and there is no FDA approved treatment to replace damaged retinal cells. Our long-term goal is to identify a safe and efficient method to generate RPE replacement cells. The hypothesis of this proposal is that a combination of defined factors can covert fibroblasts into functional iRPE. The Aims of this proposal are to 1) Utilize high-throughput assays to comprehensively screen a transcription factor library and small molecule library for candidates that can convert fibroblasts into RPE replacement cells and 2) determine if RPE replacement cells perform similarly to authentic RPE cells.